Over 500 illustrations Comprehensive coverage of biochemical diseases and related clinical information Latest advances in biochemistry and molecular medicine Harper's Illustrated Biochemistry Robert K. Murray Daryl K. Granner Peter A. Mayes twenty- Victor W. Rodwell sixth edition
a LANGE medical bookHarper'slustratedBiochemistrytwenty-sixtheditionRobertK.Murray,MD,PhDProfessor(Emeritus)ofBiochemistryUniversityofTorontoToronto,OntarioDarylK.Granner,MDJoeC.DavisProfessorofBiomedicalScienceDirector,Vanderbilt Diabetes CenterProfessorof MolecularPhysiologyand Biophysicsand of MedicineVanderbilt UniversityNashville,TennesseePeterA.Mayes,PhD,DScEmeritusProfessorofVeterinaryBiochemistryRoyalVeterinaryCollegeUniversityofLondonLondonVictor W.Rodwell,PhDProfessorof BiochemistryPurdue UniversityWest Lafayette,IndianaLange Medical Books/McGraw-HillMedical Publishing DivisionNew York Chicago San Francisco Lisbon London Madrid Mexico CityMilan New Delhi San Juan Seoul Singapore Sydney Toronto
Harper’s Illustrated Biochemistry a LANGE medical book twenty-sixth edition Robert K. Murray, MD, PhD Professor (Emeritus) of Biochemistry University of Toronto Toronto, Ontario Daryl K. Granner, MD Joe C. Davis Professor of Biomedical Science Director, Vanderbilt Diabetes Center Professor of Molecular Physiology and Biophysics and of Medicine Vanderbilt University Nashville, Tennessee Peter A. Mayes, PhD, DSc Emeritus Professor of Veterinary Biochemistry Royal Veterinary College University of London London Victor W. Rodwell, PhD Professor of Biochemistry Purdue University West Lafayette, Indiana Lange Medical Books/McGraw-Hill Medical Publishing Division New York Chicago San Francisco Lisbon London Madrid Mexico City Milan New Delhi San Juan Seoul Singapore Sydney Toronto fm01.qxd 3/16/04 11:10 AM Page i
TheMcGraw-Hill CompaniesHarper'sIllustratedBiochemistry,Twenty-SixthEditionCopyright 2003 by The McGraw-Hill Companies, Inc. All rights reserved. Printed in the United States of America. Except asPermitted under the United States Copyright Act of 1976, no part of this publication may be reproduced or distributed in anyform or by any means, or stored in a data base or retrieval system, without the prior written permission of the publisher.Previous editions copyright 2000, 1996, 1993, 1990 by Appleton & Lange; copyright 1988 by Lange Medical Publications.234567890DOC/DOC09876543ISBN0-07-138901-6ISSN 1043-9811NoticeMedicine is an ever-changing science. As new research and clinical experience broaden our knowledge, changes in treat-ment and drug therapy are required. The authors and the publisher of this work have checked with sources believed to bereliable in their efforts to provide information that is complete and generally in accord with the standards accepted at thetime of publication. However, in view of the possibility of human error or changes in medical sciences, neither the authorsnor the publisher nor any other party who has been involved in the preparation or publication of this work warrants thatthe information contained herein is in every respect accurate or complete, and they disclaim all responsibility for any er-rors or omissions or for the results obtained from use of the information contained in this work.Readers are encouragedto confirm the information contained herein with other sources. For example and in particular, readers are advised tocheck the product information sheet included in the package of each drug they plan to administer to be certain that theinformation contained in this work is accurate and that changes have not been made in the recommended dose or in thecontraindications for administration.This recommendation is of particular importance in connection with new or infre-quently used drugs.This book was set in Garamond by Pine Tree CompositionThe editors were Janet Foltin, Jim Ransom, and Janene Matragrano Oransky.The production supervisor was Phil Galea.The illustration manager was Charissa Baker.The text designer was Eve Siegel.The cover designer was Mary McKeonThe index was prepared by Kathy Pitcoff.RR Donnelley was printer and binder.This book is printed on acid-free paper.ISBN-0-07-121766-5 (International Edition)Copyright 2003. Exclusive rights by the McGraw-Hill Companies, Inc., formanufacture and export.This book cannot be re-exported from the country to which itis consigned by McGraw-Hill.The International Edition is not available in North America
Harper’s Illustrated Biochemistry, Twenty-Sixth Edition Copyright © 2003 by The McGraw-Hill Companies, Inc. All rights reserved. Printed in the United States of America. Except as permitted under the United States Copyright Act of 1976, no part of this publication may be reproduced or distributed in any form or by any means, or stored in a data base or retrieval system, without the prior written permission of the publisher. Previous editions copyright © 2000, 1996, 1993, 1990 by Appleton & Lange; copyright © 1988 by Lange Medical Publications. 234567890 DOC/DOC09876543 ISBN 0-07-138901-6 ISSN 1043-9811 Notice Medicine is an ever-changing science. As new research and clinical experience broaden our knowledge, changes in treatment and drug therapy are required. The authors and the publisher of this work have checked with sources believed to be reliable in their efforts to provide information that is complete and generally in accord with the standards accepted at the time of publication. However, in view of the possibility of human error or changes in medical sciences, neither the authors nor the publisher nor any other party who has been involved in the preparation or publication of this work warrants that the information contained herein is in every respect accurate or complete, and they disclaim all responsibility for any errors or omissions or for the results obtained from use of the information contained in this work. Readers are encouraged to confirm the information contained herein with other sources. For example and in particular, readers are advised to check the product information sheet included in the package of each drug they plan to administer to be certain that the information contained in this work is accurate and that changes have not been made in the recommended dose or in the contraindications for administration. This recommendation is of particular importance in connection with new or infrequently used drugs. This book was set in Garamond by Pine Tree Composition The editors were Janet Foltin, Jim Ransom, and Janene Matragrano Oransky. The production supervisor was Phil Galea. The illustration manager was Charissa Baker. The text designer was Eve Siegel. The cover designer was Mary McKeon. The index was prepared by Kathy Pitcoff. RR Donnelley was printer and binder. This book is printed on acid-free paper. ISBN-0-07-121766-5 (International Edition) Copyright © 2003. Exclusive rights by the McGraw-Hill Companies, Inc., for manufacture and export. This book cannot be re-exported from the country to which it is consigned by McGraw-Hill. The International Edition is not available in North America. fm01.qxd 3/16/04 11:10 AM Page ii
AuthorsDavidA.Bender,PhDPeterA.Mayes,PhD,DScSub-Dean Royal Free and University College MedicalEmeritus Professor of VeterinaryBiochemistry,RoyalSchool, Assistant Faculty Tutor and Tutor to MedVeterinary College,University ofLondonical Students,SeniorLecturerinBiochemistry,Department of Biochemistry and Molecular Biology,RobertK.Murray,MD,PhDUniversity College LondonProfessor (Emeritus) of Biochemistry,University ofTorontoKathleenM.Botham,PhD,DScReader in Biochemistry,Royal Veterinary College,Margaret L.Rand, PhDUniversity of LondonScientist, Research Institute, Hospital for Sick Chil-dren, Toronto, and Associate Professor, Depart-DarylK.Granner,MDments of Laboratory Medicine and PathobiologyJoeC.Davis Professor of Biomedical Science,Directorand Department of Biochemistry,University ofVanderbiltDiabetes Center,Professorof MolecularTorontoPhysiology and Biophysics and of Medicine, Vander-bilt University, Nashville, TennesseeVictorW.Rodwell,PhDProfessor of Biochemistry,Purdue University,WestFrederickW.Keeley,PhDLafayette, IndianaAssociateDirectorand Senior Scientist,Research Institute, Hospital for Sick Children,Toronto, and ProP.AnthonyWeil,PhDfessor,Department of Biochemistry,University ofTorontoProfessor of Molecular Physiology and Biophysics,Vanderbilt University School of Medicine,Nash-ville, TennesseePeterJ.Kennelly,PhDProfessor of Biochemistry, Virginia Polytechnic Insti-tute and State University,Blacksburg, Virginiavi
Authors David A. Bender, PhD Sub-Dean Royal Free and University College Medical School, Assistant Faculty Tutor and Tutor to Medical Students, Senior Lecturer in Biochemistry, Department of Biochemistry and Molecular Biology, University College London Kathleen M. Botham, PhD, DSc Reader in Biochemistry, Royal Veterinary College, University of London Daryl K. Granner, MD Joe C. Davis Professor of Biomedical Science, Director, Vanderbilt Diabetes Center, Professor of Molecular Physiology and Biophysics and of Medicine, Vanderbilt University, Nashville, Tennessee Frederick W. Keeley, PhD Associate Director and Senior Scientist, Research Institute, Hospital for Sick Children, Toronto, and Professor, Department of Biochemistry, University of Toronto Peter J. Kennelly, PhD Professor of Biochemistry, Virginia Polytechnic Institute and State University, Blacksburg, Virginia Peter A. Mayes, PhD, DSc Emeritus Professor of Veterinary Biochemistry, Royal Veterinary College, University of London Robert K. Murray, MD, PhD Professor (Emeritus) of Biochemistry, University of Toronto Margaret L. Rand, PhD Scientist, Research Institute, Hospital for Sick Children, Toronto, and Associate Professor, Departments of Laboratory Medicine and Pathobiology and Department of Biochemistry, University of Toronto Victor W. Rodwell, PhD Professor of Biochemistry, Purdue University, West Lafayette, Indiana P. Anthony Weil, PhD Professor of Molecular Physiology and Biophysics, Vanderbilt University School of Medicine, Nashville, Tennessee vii fm01.qxd 3/16/04 11:10 AM Page vii
PrefaceThe authors and publisher are pleased to present thetwenty-sixth edition of Harper's Illustrated Biocbemistry.Reviewof Pbysiological Chemistry was first published in 1939 and revised in 1944, and it quickly gained a wide readership. Ini95i, the third edition appeared with Harold A. Harper, University of California School of Medicine at San Fran-cisco, as author. Dr. Harper remained the sole author until the ninth edition and co-authored eight subsequent edi-tions. Peter Mayes and Victor Rodwell have been authors since the tenth edition, Daryl Granner since the twentiethedition,and Rob Murraysince thetwenty-first edition.Because of the increasing complexity ofbiochemicalknowledge,theyhaveaddedco-authorsinrecenteditionsFred Keeley and Margaret Rand have each co-authored one chapter with Rob Murray for this and previous editions. Peter Kennelly joined as a co-author in the twenty-fifth edition, and in the present edition has co-authoredwith Victor Rodwell all of the chapters dealing with the structure and function of proteins and enzymes.Thefollow-ing additional co-authors are very warmly welcomed in this edition: Kathleen Botham has co-authored, with PeterMayes, the chapters on bioenergetics, biologic oxidation, oxidative phosphorylation, and lipid metabolism. DavidBender has co-authored, also with Peter Mayes, the chapters dealing with carbohydrate metabolism, nutrition, diges-tion,and vitamins and minerals.P.AnthonyWeil has co-authored chapters dealing with various aspects of DNA, ofRNA, and ofgene expression with Daryl Granner.We are all very grateful to our co-authors for bringing their ex-pertise and fresh perspectives to the text.CHANGESINTHETWENTY-SIXTHEDITIONA major goal of the authors continues to beto provideboth medical and other students of the health sciences with abook that both describes the basics of biochemistry and is user-friendly and interesting.A second major ongoinggoal is to reflect the most significant advances in biochemistry that are important to medicine. However, a thirdmajor goal ofthis edition was to achieve a substantial reduction in size,as feedback indicated that many readers prefershortertextsTo achieve this goal, all of the chapters were rigorously edited, involving their amalgamation, division, or deletion, and many werereduced to approximately one-half to two-thirds of their previous size.This has been effectedwithout loss of crucial information but with gain in conciseness and clarity.Despite the reduction in size, there are many new features in the twenty-sixth edition. These include: A new chapter on amino acids and peptides, which emphasizes the manner in which the properties of biologicpeptides derive from the individual amino acids of which they are comprised. A new chapter on the primary structure of proteins, which provides coverage of both classic and newly emerging"proteomic"and"genomic"methods for identifying proteins.A new section on the application of mass spectrometryto the analysis of protein structure has been added, including comments on the identification of covalent modifica-tions.:The chapter on the mechanisms of action of enzymes has been revised to provide a comprehensive description ofthe various physical mechanisms by which enzymes carry out their catalytic functions..The chapters on integration ofmetabolism,nutrition,digestion and absorption, and vitamins and minerals havebeen completely re-written.Among importantadditions to the various chapters on metabolism are thefollowing:update ofthe informationon oxidative phosphorylation,includinga description of the rotaryATP synthase;new insights into the role ofGTP in gluconeogenesis; additional information on the regulation ofacetyl-CoA carboxylase; new information onreceptors involved in lipoprotein metabolism and reverse cholesterol transport; discussion of the role of leptin infat storage; and new information on bile acid regulation, including the role of the farnesoid X receptor (FXR).·The chapter on membranebiochemistryin theprevious editionhasbeen splitinto two,yielding two newchapterson thestructureand function of membranes and intracellular traffic and sorting of proteins. Considerable new material has been added on RNA synthesis, protein synthesis, gene regulation, and various aspects of molecular genetics.:Much of the material on individual endocrine glands present in the twenty-fifth edition has been replaced withnew chapters dealing with the diversity of the endocrine system, with molecular mechanisms of hormone action,and with signal transduction.ix
Preface ix The authors and publisher are pleased to present the twenty-sixth edition of Harper’s Illustrated Biochemistry. Review of Physiological Chemistry was first published in 1939 and revised in 1944, and it quickly gained a wide readership. In 1951, the third edition appeared with Harold A. Harper, University of California School of Medicine at San Francisco, as author. Dr. Harper remained the sole author until the ninth edition and co-authored eight subsequent editions. Peter Mayes and Victor Rodwell have been authors since the tenth edition, Daryl Granner since the twentieth edition, and Rob Murray since the twenty-first edition. Because of the increasing complexity of biochemical knowledge, they have added co-authors in recent editions. Fred Keeley and Margaret Rand have each co-authored one chapter with Rob Murray for this and previous editions. Peter Kennelly joined as a co-author in the twenty-fifth edition, and in the present edition has co-authored with Victor Rodwell all of the chapters dealing with the structure and function of proteins and enzymes. The following additional co-authors are very warmly welcomed in this edition: Kathleen Botham has co-authored, with Peter Mayes, the chapters on bioenergetics, biologic oxidation, oxidative phosphorylation, and lipid metabolism. David Bender has co-authored, also with Peter Mayes, the chapters dealing with carbohydrate metabolism, nutrition, digestion, and vitamins and minerals. P. Anthony Weil has co-authored chapters dealing with various aspects of DNA, of RNA, and of gene expression with Daryl Granner. We are all very grateful to our co-authors for bringing their expertise and fresh perspectives to the text. CHANGES IN THE TWENTY-SIXTH EDITION A major goal of the authors continues to be to provide both medical and other students of the health sciences with a book that both describes the basics of biochemistry and is user-friendly and interesting. A second major ongoing goal is to reflect the most significant advances in biochemistry that are important to medicine. However, a third major goal of this edition was to achieve a substantial reduction in size, as feedback indicated that many readers prefer shorter texts. To achieve this goal, all of the chapters were rigorously edited, involving their amalgamation, division, or deletion, and many were reduced to approximately one-half to two-thirds of their previous size. This has been effected without loss of crucial information but with gain in conciseness and clarity. Despite the reduction in size, there are many new features in the twenty-sixth edition. These include: • A new chapter on amino acids and peptides, which emphasizes the manner in which the properties of biologic peptides derive from the individual amino acids of which they are comprised. • A new chapter on the primary structure of proteins, which provides coverage of both classic and newly emerging “proteomic” and “genomic” methods for identifying proteins. A new section on the application of mass spectrometry to the analysis of protein structure has been added, including comments on the identification of covalent modifications. • The chapter on the mechanisms of action of enzymes has been revised to provide a comprehensive description of the various physical mechanisms by which enzymes carry out their catalytic functions. • The chapters on integration of metabolism, nutrition, digestion and absorption, and vitamins and minerals have been completely re-written. • Among important additions to the various chapters on metabolism are the following: update of the information on oxidative phosphorylation, including a description of the rotary ATP synthase; new insights into the role of GTP in gluconeogenesis; additional information on the regulation of acetyl-CoA carboxylase; new information on receptors involved in lipoprotein metabolism and reverse cholesterol transport; discussion of the role of leptin in fat storage; and new information on bile acid regulation, including the role of the farnesoid X receptor (FXR). • The chapter on membrane biochemistry in the previous edition has been split into two, yielding two new chapters on the structure and function of membranes and intracellular traffic and sorting of proteins. • Considerable new material has been added on RNA synthesis, protein synthesis, gene regulation, and various aspects of molecular genetics. • Much of the material on individual endocrine glands present in the twenty-fifth edition has been replaced with new chapters dealing with the diversity of the endocrine system, with molecular mechanisms of hormone action, and with signal transduction. fm01.qxd 3/16/04 11:10 AM Page ix